Hexachlorophene (HCP) causes reversible myelinopathy of central and peripheral myelin. Our previous studies showed a gradient of regional vulnerability in the CNS, irreversible axonal degeneration in the optic nerves and hydrocephalus ex vacuo in chronically intoxicated rats. This experimental model will now be used to extend our understanding of the pathogenesis of these changes and also to study possible correlations between the biochemical and morphological changes. Whole brain composition and myelin content and its lipid and protein composition will be studied during HCP intoxication using standard methods of lipid analysis and discontinuous gel electrophoresis for separation of myelin proteins. These studies will be repeated after withdrawal of HCP to determine whether full qualitative and quantitative recovery of myelin has taken place. The mechanism of HCP action will be explored by studying the activities of a selected group of enzymes which might be specifically depressed by HCP: (a) Those concerned with ion transport across membranes; (b) an enzyme specific for myelin; (c) an enzyme specific for glia. Since HCP uncouples oxidative phosphorylation one aspect of brain energy metabolism will be investigated by measuring O2 uptake in isolated brain mitochondria using a polarographic technique. The distribution of C14- labelled HCP in brain subcellular fractions will be determined in order to localize its binding site(s). The effect of HCP on memebranes other than myelin will be studied by doing lipid and protein analysis of liver mitochondria.